phase iii randomized study of anti-tumor necrosis factor chimeric monoclonal antibody (ca2) for patients with enterocutaneous fistulae as a complication of crohn's disease

Conditions: Crohn's Disease

Summary: objectives: i. evaluate the efficacy of chimeric monoclonal antibody (ca2) compared with placebo in closure of enterocutaneous fistulae in patients with crohn's disease.

protocol outline: this is a randomized, double blind, placebo controlled, multicenter study. patients are stratified according to investigational site and number of fistulae (single vs multiple). patients are randomized to one of three treatment arms: arm i: patients receive an infusion of chimeric monoclonal antibody (ca2) on weeks 0, 2, and 6. arm ii: patients receive an infusion of ca2 on weeks 0 and 2, and an infusion of placebo on week 6. arm iii: patients receive an infusion of placebo on day 1 of weeks 0, 2, and 6. patients are followed every month for 3 months, then every 6-12 months for up to 2 years.

Eligibility criteria:
protocol entry criteria: --disease characteristics-- crohn's disease of at least 3 months duration confirmed by radiography or endoscopy single or multiple draining enterocutaneous (including perianal) fistulae of at least 3 months duration all fistulae separate and distinctly identifiable no local complications of crohn's disease such as strictures or abscesses --prior/concurrent therapy-- biologic therapy: * no prior chimeric monoclonal antibody (ca2) * at least 3 months since treatment with other therapeutic agent targeted at reducing tumor necrosis factor (e.g., pentoxifylline or thalidomide) * at least 4 weeks since cyclosporine chemotherapy: * concurrent methotrexate permitted if treatment began at least 3 months prior to enrollment, dose has been stable for at least 4 weeks prior to enrollment and remains stable throughout study period * otherwise, no methotrexate within 4 weeks prior to enrollment concurrent 6-mercaptopurine or azathioprine permitted if treatment began at least 6 months prior to enrollment, dose has been stable for at least 8 weeks prior to enrollment, and remains stable throughout study period otherwise, no 6-mercaptopurine or azathioprine within 4 weeks prior to enrollment endocrine therapy: * concurrent corticosteroids (e.g., oral prednisone) permitted if dose has been stable for at least 3 weeks prior to enrollment, does not exceed 40 mg/kg, and remains stable throughout study period (dosage may be tapered after 6 weeks for some patients) * otherwise, no corticosteroids within 4 weeks prior to enrollment other: * concurrent antibiotics or aminosalicylates for crohn's disease permitted if dose has been stable for at least 4 weeks prior to enrollment and remains stable throughout study period * otherwise, no antibiotics or aminosalicylates within 4 weeks prior to enrollment * at least 3 months since investigational drugs --patient characteristics-- hematopoietic: * wbc at least 3,500/mm3 * neutrophil count at least 1,500/mm3 * lymphocyte count at least 500/mm3 * platelet count at least 100,000/mm3 * hemoglobin at least 8.5 g/dl * no severe, progressive, or uncontrolled hematologic disease hepatic: * sgot no greater than 3 times upper limit of normal (uln) * alkaline phosphatase no greater than 3 times uln * no severe, progressive, or uncontrolled hepatic disease renal: * creatinine no greater than 1.7 mg/dl * no severe, progressive, or uncontrolled renal disease cardiovascular: no severe, progressive, or uncontrolled cardiac disease pulmonary: no severe, progressive, or uncontrolled pulmonary disease neurologic: no severe, progressive, or uncontrolled neurologic or cerebral disease other: * negative pregnancy test required and no planned pregnancy within 7.5 months following first infusion * effective contraception required of fertile patients during and for 6 months after study * no severe, progressive, or uncontrolled endocrine disease * no serious infections (e.g., hepatitis, pneumonia, pyelonephritis) within prior 3 months * no history of opportunistic infections (e.g., herpes zoster) within 2 months * no allergy to murine proteins * no active cytomegalovirus, pneumocystis carinii, or drug resistant atypical mycobacterial infections * no recent drug or alcohol abuse * no hiv infection, arc (aids-related complex) or aids * total parenteral nutrition or tube feeding not permitted * no prior or concurrent malignancy within 5 years

Keywords: crohn's disease gastrointestinal disorders rare disease